{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:19:00Z","timestamp":1787894340490,"version":"build-2784847793"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Ka 502\/19-3, EXC294, EXC 2189,  SFB1381 (A9), SCHA-976\/8-1, FOR 2799, GSC-4"],"award-info":[{"award-number":["Ka 502\/19-3, EXC294, EXC 2189,  SFB1381 (A9), SCHA-976\/8-1, FOR 2799, GSC-4"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100021828","name":"German Academic Exchange Service","doi-asserted-by":"publisher","award":["Longterm fellowship"],"award-info":[{"award-number":["Longterm fellowship"]}],"id":[{"id":"10.13039\/100021828","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2019\/35\/N\/NZ6\/02973"],"award-info":[{"award-number":["2019\/35\/N\/NZ6\/02973"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    \u03b3\u03b4 T cells have raised interest as effector cells in cancer immunotherapy, due to their broad and HLA-independent reactivity towards multiple tumor entities. Despite promising ongoing clinical studies, there is a need to improve the effector function and thereby the efficacy of \u03b3\u03b4 T cells. In addition to its role as anti-oxidant, Vitamin C is an epigenetic modifier and exerts multiple effects on T-cell differentiation. While Vitamin C enhances\n                    <jats:italic>in vitro<\/jats:italic>\n                    proliferation, cytokine production and cytotoxicity of \u03b3\u03b4 T cells, the associated signaling pathways have so far not been elucidated. Here we demonstrate that Vitamin C enhances the cytotoxic effector function of unmodified as well as anti-CD19 chimeric antigen receptor (CAR) and TCR fusion construct (\u03b5TRuC)-transduced zoledronate-expanded \u03b3\u03b4 T cells. This was associated with increased upregulation of CD25 and IFN-\u03b3 secretion. Vitamin C increased calcium influx and nuclear translocation of NFAT and NF-\u03baB in short-term expanded \u03b3\u03b4 T-cell lines. Although Vitamin C did not alter CD3\u03b6 phosphorylation following stimulation with anti-CD3 antibodies, it reduced phosphorylation of ERK1\/2 without affecting p38 MAP kinases. Further analysis showed that Vitamin C did not modulate the expression of selected immune checkpoint molecules on \u03b3\u03b4 T cells. Our results identify important signaling events where Vitamin C enhances the effector activity of human \u03b3\u03b4 T cells.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1759941","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T04:33:04Z","timestamp":1787891584000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Vitamin C enhances cytotoxicity of CAR-and \u03b5TRuC-engineered \u03b3\u03b4 T cells and modulates Ca2+, NFAT, NF-\u03baB and ERK signaling in human \u03b3\u03b4 T cells"],"prefix":"10.3389","volume":"17","author":[{"given":"Michal","family":"Zarobkiewicz","sequence":"first","affiliation":[{"name":"Institute of Medical Immunology, Christian-Albrechts University, University Hospital Schleswig-Holstein","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Ma","sequence":"additional","affiliation":[{"name":"Signalling Research Centres BIOSS and CIBSS, Faculty of Biology, University of Freiburg","place":["Freiburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Juraske","sequence":"additional","affiliation":[{"name":"Signalling Research Centres BIOSS and CIBSS, Faculty of Biology, University of Freiburg","place":["Freiburg, Germany"]},{"name":"Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg","place":["Freiburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Cierna","sequence":"additional","affiliation":[{"name":"Institute of Medical Immunology, Christian-Albrechts University, University Hospital Schleswig-Holstein","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9once","family":"Kouakanou","sequence":"additional","affiliation":[{"name":"Institute of Medical Immunology, Christian-Albrechts University, University Hospital Schleswig-Holstein","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia Maria","family":"Kri\u00dfmer","sequence":"additional","affiliation":[{"name":"Signalling Research Centres BIOSS and CIBSS, Faculty of Biology, University of Freiburg","place":["Freiburg, Germany"]},{"name":"Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg","place":["Freiburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina J.","family":"Fiala","sequence":"additional","affiliation":[{"name":"Signalling Research Centres BIOSS and CIBSS, Faculty of Biology, University of Freiburg","place":["Freiburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Peters","sequence":"additional","affiliation":[{"name":"Institute of Medical Immunology, Christian-Albrechts University, University Hospital Schleswig-Holstein","place":["Kiel, Germany"]},{"name":"Cyto Kiel, Cytometry Core Facility, Christian-Albrechts University, University Hospital Schleswig-Holstein","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang W.","family":"Schamel","sequence":"additional","affiliation":[{"name":"Signalling Research Centres BIOSS and CIBSS, Faculty of Biology, University of Freiburg","place":["Freiburg, Germany"]},{"name":"Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg","place":["Freiburg, Germany"]},{"name":"Centre for Chronic Immunodeficiency (CCI), Medical Centre Freiburg, Faculty of Medicine, University of Freiburg","place":["Freiburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Kabelitz","sequence":"additional","affiliation":[{"name":"Institute of Medical Immunology, Christian-Albrechts University, University Hospital Schleswig-Holstein","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1080\/10715760500104025","article-title":"Review: When is an antioxidant not an antioxidant? A review of novel actions and reactions of vitamin C","volume":"39","author":"Duarte","year":"2005","journal-title":"Free Radic Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102753","article-title":"Vitamin C: From nutrition to oxygen sensing and epigenetics","volume":"63","author":"Kietzmann","year":"2023","journal-title":"Redox Biol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-071714-034228","article-title":"Regulation of the epigenome by vitamin C","volume":"35","author":"Young","year":"2015","journal-title":"Annu Rev Nutr"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00210","article-title":"TET enzymes and 5hmC in adaptive and innate immune systems","volume":"10","author":"Lio","year":"2019","journal-title":"Front Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/bies.202300035","article-title":"Ascorbic acid modulates immune responses through Jumonji-C domain containing histone demethylases and Ten eleven translocation (TET) methylcytosine dioxygenase","volume":"45","author":"Maity","year":"2023","journal-title":"Bioessays"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1TA0214-121RR","article-title":"Technical advance: Ascorbic acid induces development of double-positive T cells from human hematopoietic stem cells in the absence of stromal cells","volume":"96","author":"Huijskens","year":"2014","journal-title":"J Leukoc Biol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2010.10.005","article-title":"Vitamin C-treated murine bone marrow-derived dendritic cells preferentially drive na\u00efve T cells into Th1 cells by increased IL-12 secretions","volume":"266","author":"Jeong","year":"2011","journal-title":"Cell Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151438","article-title":"Control of Foxp3 stability through modulation of TET activity","volume":"213","author":"Yue","year":"2016","journal-title":"J Exp Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.1MR1219-245R","article-title":"A comparative view on vitamin C effects on \u03b1\u03b2- versus \u03b3\u03b4 T-cell activation and differentiation","volume":"107","author":"Peters","year":"2020","journal-title":"J Leukoc Biol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1556\/1886.2024.00017","article-title":"Impact of vitamin C on the development, differentiation and functional properties of T cells","volume":"14","author":"Sasidharan Nair","year":"2024","journal-title":"Eur J Microbiol Immunol (Bp)"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202451028","article-title":"Empowering \u03b3\u03b4 T-cell functionality with vitamin C","volume":"54","author":"Kabelitz","year":"2024","journal-title":"Eur J Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa5004","article-title":"Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH","volume":"350","author":"Yun","year":"2015","journal-title":"Science"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay8707","article-title":"High-dose vitamin C enhances cancer immunotherapy","volume":"12","author":"Magr\u00ec","year":"2020","journal-title":"Sci Transl Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0504-x","article-title":"Cancer immunotherapy with \u03b3\u03b4 T cells: Many paths ahead of us","volume":"17","author":"Kabelitz","year":"2020","journal-title":"Cell Mol Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-022-00722-1","article-title":"The emerging roles of \u03b3\u03b4 T cells in cancer immunotherapy","volume":"20","author":"Mensurado","year":"2023","journal-title":"Nat Rev Clin Oncol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1126\/science.abq7248","article-title":"Cancer immunotherapy by \u03b3\u03b4 T cells","volume":"386","author":"Hayday","year":"2024","journal-title":"Science"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202451068","article-title":"Phosphoantigen recognition by V\u03b39V\u03b42 T cells","author":"Herrmann","year":"2024","journal-title":"Eur J Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021500","article-title":"Human T cell receptor gammadelta cells recognize endogenous mevalonate metabolites in tumor cells","volume":"197","author":"Gober","year":"2003","journal-title":"J Exp Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-019-0247-8","article-title":"Vitamin C promotes the proliferation and effector functions of human \u03b3\u03b4 T cells","volume":"17","author":"Kouakanou","year":"2020","journal-title":"Cell Mol Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"6550","DOI":"10.1038\/s41598-020-63572-w","article-title":"Vitamin C supports conversion of human \u03b3\u03b4 T cells into FOXP3-expressing regulatory cells by epigenetic regulation","volume":"10","author":"Kouakanou","year":"2020","journal-title":"Sci Rep"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0515-7","article-title":"Allogeneic V\u03b39V\u03b42 T-cell immunotherapy exhibits promising clinical safety and prolongs the survival of patients with late-stage lung or liver cancer","volume":"18","author":"Xu","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1056\/NEJMra1706169","article-title":"Chimeric antigen receptor therapy","volume":"379","author":"June","year":"2018","journal-title":"N Engl J Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nature22395","article-title":"Therapeutic T cell engineering","volume":"545","author":"Sadelain","year":"2017","journal-title":"Nature"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1016\/j.cell.2018.03.038","article-title":"Universal chimeric antigen receptors for multiplexed and logical control of T cell responses","volume":"173","author":"Cho","year":"2018","journal-title":"Cell"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2678","article-title":"Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy","volume":"31","author":"Themeli","year":"2013","journal-title":"Nat Biotechnol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.1038\/s41467-019-10097-0","article-title":"Synthetic TRuC receptors engaging the complete T cell receptor for potent anti-tumor response","volume":"10","author":"Baeuerle","year":"2019","journal-title":"Nat Commun"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-024-01093-7","article-title":"From TCR fundamental research to innovative chimeric antigen receptor design","volume":"25","author":"Minguet","year":"2025","journal-title":"Nat Rev Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2005650","article-title":"Conformational changes in the T cell receptor differentially determine T cell subset development in mice","volume":"7","author":"Blanco","year":"2014","journal-title":"Sci Signal"},{"key":"B29","doi-asserted-by":"publisher","first-page":"47","DOI":"10.4049\/jimmunol.1601661","article-title":"The allostery model of TCR regulation","volume":"198","author":"Schamel","year":"2017","journal-title":"J Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.04.049","article-title":"The CD3 conformational change in the \u03b3\u03b4 T cell receptor is not triggered by antigens but can be enforced to enhance tumor killing","volume":"7","author":"Dopfer","year":"2014","journal-title":"Cell Rep"},{"key":"B31","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1093\/jleuko\/qiad128","article-title":"Reprogramming of human \u03b3\u03b4 T cells by expression of an anti-CD19 TCR fusion construct (\u03f5TRuC) to enhance tumor killing","volume":"115","author":"Juraske","year":"2024","journal-title":"J Leukoc Biol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-25-0005","article-title":"Vitamin C conditioning generates tumor-targeting CAR T cells with superior cytotoxicity and fitness in a posttransplant lymphoproliferative disorder tumor model","volume":"25","author":"Rahmati","year":"2026","journal-title":"Mol Cancer Ther"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mie.2019.07.019","article-title":"In vitro expansion of V\u03b39V\u03b42 T cells for immunotherapy","volume":"631","author":"Peters","year":"2020","journal-title":"Methods Enzymol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2022.2030021","article-title":"Stimulatory and inhibitory activity of STING ligands on tumor-reactive human gamma\/delta T cells","volume":"11","author":"Serrano","year":"2022","journal-title":"Oncoimmunology"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.11.6767","article-title":"Characterization of tumor reactivity of human V gamma 9V delta 2 gamma delta T cells in vitro and in SCID mice in vivo","volume":"173","author":"Kabelitz","year":"2004","journal-title":"J Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-01855-4","article-title":"Perinatal thymic-derived CD8\u03b1\u03b2-expressing \u03b3\u03b4 T cells are innate IFN-\u03b3 producers that expand in IL-7R-STAT5B-driven neoplasms","volume":"25","author":"Sumaria","year":"2024","journal-title":"Nat Immunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.ade3525","article-title":"NK-like CD8+ \u03b3\u03b4 T cells are expanded in persistent Mycobacterium tuberculosis infection","volume":"8","author":"Roy Chowdhury","year":"2023","journal-title":"Sci Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601146","article-title":"CD8\u03b1\u03b2+ \u03b3\u03b4 T cells: A novel T cell subset with a potential role in inflammatory bowel disease","volume":"197","author":"Kadivar","year":"2016","journal-title":"J Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.37349\/ei.2022.00042","article-title":"Augmenting human gamma delta lymphocytes for cancer therapy with chimeric antigen receptors","volume":"2","author":"Ferry","year":"2022","journal-title":"Explor Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2012.267","article-title":"Bispecific T-cells expressing polyclonal repertoire of endogenous \u03b3\u03b4 T-cell receptors and introduced CD19-specific chimeric antigen receptor","volume":"21","author":"Deniger","year":"2013","journal-title":"Mol Ther"},{"key":"B41","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1038\/s41568-025-00830-x","article-title":"Disrupting the balance between activating and inhibitory receptors of \u03b3\u03b4T cells for effective cancer immunotherapy","volume":"25","author":"Beringer","year":"2025","journal-title":"Nat Rev Cancer"},{"key":"B42","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/s41392-021-00823-w","article-title":"T cell receptor (TCR) signaling in health and disease","volume":"6","author":"Shah","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.2MR1219-233R","article-title":"\u03b1\u03b2 and \u03b3\u03b4 T cell receptors: Similar but different","volume":"107","author":"Morath","year":"2020","journal-title":"J Leukoc Biol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.111321","article-title":"High dose vitamin C inhibits PD-L1 by ROS-pSTAT3 signal pathway and enhances T cell function in TNBC","volume":"126","author":"Zhao","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.cophys.2020.07.016","article-title":"Calcium regulation of T cell metabolism","volume":"17","author":"Wang","year":"2020","journal-title":"Curr Opin Physiol"},{"key":"B46","article-title":"Vitamin C decreases intracellular calcium level in human lymphoid cells","volume":"52","author":"Ozt\u00fcrk","year":"2001","journal-title":"J Physiol Pharmacol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac941","article-title":"Vitamin C enhances NF-\u03baB-driven epigenomic reprogramming and boosts the immunogenic properties of dendritic cells","volume":"50","author":"Morante-Palacios","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"B48","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.bbrc.2022.04.103","article-title":"Enhancement of vitamin C-induced myogenesis by inhibition of extracellular signal-regulated kinase (ERK) 1\/2 pathway","volume":"612","author":"Fu","year":"2022","journal-title":"Biochem Biophys Res Commun"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.7150\/thno.35219","article-title":"Vitamin C kills thyroid cancer cells through ROS-dependent inhibition of MAPK\/ERK and PI3K\/AKT pathways via distinct mechanisms","volume":"9","author":"Su","year":"2019","journal-title":"Theranostics"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01050.2003","article-title":"Protein phosphatase 2A-mediated cross-talk between p38 MAPK and ERK in apoptosis of cardiac myocytes","volume":"286","author":"Liu","year":"2004","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1017340108","article-title":"T-cell receptor ligation induces distinct signaling pathways in naive vs. antigen-experienced T cells","volume":"108","author":"Adachi","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600268","article-title":"Negative feedback loop in T-cell activation through MAPK-catalyzed threonine phosphorylation of LAT","volume":"23","author":"Matsuda","year":"2004","journal-title":"EMBO J"},{"key":"B53","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1042\/BCJ20200661","article-title":"Extracellular signal-regulated kinase (ERK) pathway control of CD8+ T cell differentiation","volume":"478","author":"Damasio","year":"2021","journal-title":"Biochem J"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxw037","article-title":"Cell cycle arrest caused by MEK\/ERK signaling is a mechanism for suppressing growth of antigen-hyperstimulated effector T cells","volume":"28","author":"Ohtsuka","year":"2016","journal-title":"Int Immunol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1186\/s13046-021-02134-y","article-title":"High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer","volume":"40","author":"B\u00f6ttger","year":"2021","journal-title":"J Exp Clin Cancer Res"},{"key":"B56","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1007\/s00520-026-10434-2","article-title":"High-dose vitamin C supplementation in patients undergoing allogeneic hematopoietic stem cell transplantation: A pilot randomized, triple-blind, placebo-controlled trial","volume":"34","author":"Heidari","year":"2026","journal-title":"Support Care Cancer"},{"key":"B57","doi-asserted-by":"publisher","first-page":"1858","DOI":"10.1016\/j.cell.2025.01.043","article-title":"Lysine vitcylation is a vitamin C-derived protein modification that enhances STAT1-mediated immune response","volume":"188","author":"He","year":"2025","journal-title":"Cell"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114695","article-title":"Cell signaling pathways based on vitamin C and their application in cancer therapy","volume":"162","author":"Fan","year":"2023","journal-title":"BioMed Pharmacother"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.2174\/1568026620666200710102841","article-title":"Vitamin C as an anticancer agent: Regulation of signaling pathways","volume":"20","author":"Butt","year":"2020","journal-title":"Curr Top Med Chem"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1512605","article-title":"High-dose ascorbic acid synergizes with anti-PD1 therapy in non-small cell lung cancer in vitro and in vivo models","volume":"15","author":"Kim","year":"2025","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1759941\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T04:33:08Z","timestamp":1787891588000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1759941\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":60,"alternative-id":["10.3389\/fimmu.2026.1759941"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1759941","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]},"article-number":"1759941"}}